title: Role of the Vibrio cholerae matrix protein Bap1 in cross-resistance to antimicrobial peptides.
abstract: Outer membrane vesicles (OMVs) that are released from Gram-negative pathogenic bacteria can serve as vehicles for the translocation of effectors involved in infectious processes. In this study we have investigated the role of OMVs of the Vibrio cholerae O1 El Tor A1552 strain in resistance to antimicrobial peptides (AMPs). To assess this potential role, we grew V. cholerae with sub-lethal concentrations of Polymyxin B (PmB) or the AMP LL-37 and analyzed the OMVs produced and their effects on AMP resistance. Our results show that growing V. cholerae in the presence of AMPs modifies the protein content of the OMVs. In the presence of PmB, bacteria release OMVs that are larger in size and contain a biofilm-associated extracellular matrix protein (Bap1). We demonstrated that Bap1 binds to the OmpT porin on the OMVs through the LDV domain of OmpT. In addition, OMVs from cultures incubated in presence of PmB also provide better protection for V. cholerae against LL-37 compared to OMVs from V. cholerae cultures grown without AMPs or in presence of LL-37. Using a bap1 mutant we showed that cross-resistance between PmB and LL-37 involved the Bap1 protein, whereby Bap1 on OMVs traps LL-37 with no subsequent degradation of the AMP.
authors.affiliation: Department of Molecular Biology, The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
authors.forename: Marylise
authors.initials: M
authors.lastname: Duperthuy
authors.forename: Annika E
authors.initials: AE
authors.lastname: Sjöström
authors.forename: Dharmesh
authors.initials: D
authors.lastname: Sabharwal
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Damghani
authors.forename: Bernt Eric
authors.initials: BE
authors.lastname: Uhlin
authors.forename: Sun Nyunt
authors.initials: SN
authors.lastname: Wai
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D018272:Porins / Q000235:genetics / Q000378:metabolism*; D014734:Vibrio cholerae / Q000235:genetics / Q000378:metabolism*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D016326:Extracellular Matrix Proteins; D018272:Porins; C405564:ompT protein, bacteria; D054804:Cathelicidins